of 31
8/13/2019 Razel (New) 25072013
1/31
RAZEL
8/13/2019 Razel (New) 25072013
2/31
CAD in India
(IHD) or CAD) is affecting the Indianpopulation like an epidemic in this new
millennium
CAD is affecting Indians 5-10 years earlierthan other countries
The risk of CAD in Indians is 3-4 times
higher than White Americans, 6-timeshigher than Chinese, and 20-times higher
than Japanese
8/13/2019 Razel (New) 25072013
3/31
CAD in India
South Indians have higher prevalence, 7
percent in rural and 14 percent in urban
areas.
Deaths attributed to cardiovascular
disease would double in India in the year
1985-2015. (from 11.6% to 33.6%)
8/13/2019 Razel (New) 25072013
4/31
LDL-C as the Major
Risk Factor NCEP (ATP III guideline) still
recognizes LDL-C as the number one
risk factor in the development ofatherosclerosis
LDL-C is the primary goal in
management of dyslipidemia.
8/13/2019 Razel (New) 25072013
5/31
(2001 National Cholesterol Education
Program Guidelines)
Goal mg/dL
Drug Therapy
No CHD and 0-1 risk factors
8/13/2019 Razel (New) 25072013
6/31
Statins in Dyslipidemia
Excellent tolerability and positive
impact on morbidity and mortality
makes statins first choice for most
patients with dyslipidemia.
8/13/2019 Razel (New) 25072013
7/31
Some important studies
of Statins
8/13/2019 Razel (New) 25072013
8/31
Need of a SUPER STATIN
Higher Potency Reducing triglyceride level also
Increase in HDL
Management of Severe / Familialhyperlipidemia
More hepatoselectivity
Diabetic dyslipidemia Emergence of non-HDL cholesterols and
ApoB as atherogens
Drug-drug interactions
8/13/2019 Razel (New) 25072013
9/31
Properties of an Ideal Statin
Effectively reduce LDL-C (NCEP goal) at therecommended starting dose
Should effectively reduce triglycerides, non
HDL-C and ApoB and increase HDL.
Should be more potent to ensure maximum
inhibition of HMG CoA reductase
Hepato-selective.
Optimal pharmacokinetics (relation to food, time
of administration during anytime of the day).
Less potential for drug-drug interactions
8/13/2019 Razel (New) 25072013
10/31
RAZEL (Rosuvastatin)
First statins to be introduced was Lovastatin,followed by Pravastatin, Fluvastatin, Simvastatin
and Atorvastatin.
We have introduced the latest statin
Rosuvastatin, which is also learned as superstatin, for the first time in India.
Cerivastatin was withdrawn due to high
incidence of rhabdomyolysis We also have introduced the most powerful
statin, called the SUPER STATIN
Rosuvastatin
8/13/2019 Razel (New) 25072013
11/31
Description
Rosuvastatin (RAZEL) is a totally synthetic,
orally active molecule containing a novelseries of methane-sulfonamide group,
which makes it more hydrophilicthan other
statins.
US FDA has approved Rosuvastatin
8/13/2019 Razel (New) 25072013
12/31
Mode of action
Acetyl CoA + Acetyl CoA
Acetoacetyl CoA
HMG CoA (3 - H ydroxy3 - methylglutaryl CoA )
Mevalonic acid
Cholesterol
RAZELHMG CoAreductase
8/13/2019 Razel (New) 25072013
13/31
Mode of Action Causes upregulation of LDL cholesterol
receptors in the liver, thereby increasingclearance of LDL cholesterol from the plasma.
Affect LDL production by decreasing hepatic
production of VLDL and by increasing
catabolism of VLDL remnants
Interfere with the hepatic formation of
lipoproteins by reducing cholesterol synthesis.
RAZEL increase HDL.
RAZEL exerted anti-inflammatory
8/13/2019 Razel (New) 25072013
14/31
Pharmacological actions
Potency (highest) Hepato-selectivity (High)
Action on LDL-C (upto 65%)
LDL Reduction Simvastatin Atorvastatin Rosuvastatin
< 25% 5 10 5
25-35% 10-20 10 5
35-45% 20-40 10-20 5-1045-55% 80 20-40 10-20
55-60% 80 20-40
60-65% 80
8/13/2019 Razel (New) 25072013
15/31
Pharmacological Actions
Action on triglycerides (upto 40%)
Action on HDL (upto 13%); in fact HDL
decreases with increase in Atorvastatindose.
Action on ApoB and non HDL-C
Action on Metabolic Syndrome
Pleotropic effectreduce MMP
8/13/2019 Razel (New) 25072013
16/31
Pharmacokinetics
8/13/2019 Razel (New) 25072013
17/31
Indications
US FDA has approved Rosuvastatin for
the treatment of dyslipidemia.
RAZEL is recommended as an adjunct todiet and exercise for the treatment of
various lipid disorders including
Hypercholesterolemia Mixed dyslipidemia and
Isolated hypertriglyceridemia
8/13/2019 Razel (New) 25072013
18/31
Dosage
Usual starting dose is 5-10 mg once daily
Adjustment to 20 mg can be made after 4
weeks, if necessary.
Rosuvastatin 40 mg should only be used in
patients with severe hypercholesterolemias
who do not achieve their treatment goal on 20mg.
Rosuvastatin may be given at any time of day,
with or without food.
8/13/2019 Razel (New) 25072013
19/31
Adverse effects
RAZEL is very well tolerated compared to
other statins.
The most common adverse effectsreported are pharyngitis, pain, headache,
flue syndrome, myalgia.
Rhabdomyolysis has been reported withonly 80 mg dose (0.2%)
8/13/2019 Razel (New) 25072013
20/31
Contraindications
Hypersensitivity to Rosuvastatin
Pregnant and Nursing mothers
8/13/2019 Razel (New) 25072013
21/31
Precautions
Patients with history of
hypersensitivity to other statins.
Patients with liver disease
Patients with myopathy.
Patients receiving concomitant
cyclosporine.
8/13/2019 Razel (New) 25072013
22/31
Precaution
Carcinogenesis, mutagenesis, impairment
of fertility
Not reported
Pregnancy
Safety has not been established
Nursing Mothers
Safety has not been established
8/13/2019 Razel (New) 25072013
23/31
Precautions
Pediatric Use Pediatric experience is limited to a small number of children
(aged 8 years or above) with homozygous familial
hypercholesterolemia.
Special populations:
Age and sex:
No clinically relevant effect on the pharmacokinetics of
Rosuvastatin.
Renal insufficiency:
Pharmacokinetics is not affected by mild to moderate renal
impairment.
Hepatic insufficiency:
The pharmacokinetics is not affected by mild to moderate
hepatic impairment.
8/13/2019 Razel (New) 25072013
24/31
Drug Interactions
Cytochrome P450 2C9 and 2C19 are
the primary metabolic enzymes
No significant drug interactions has
been observed
8/13/2019 Razel (New) 25072013
25/31
Features & Benefits
8/13/2019 Razel (New) 25072013
26/31
Features & Benefits
8/13/2019 Razel (New) 25072013
27/31
Rosuvastatin: Salient Features Selective and competitive inhibitor of HMG-CoA
reductase
Most potent HMG-CoA inhibitor (statin)
Hepatoselective statin- Less lipophilic than atorvastatin,
simvastatin, lovastatin and fluvastatin
Cardioprotective, vasoprotective and anti-inflammatory
actions independent of its lipid lowering properties
Limited systemic availability
No metabolism by CYP 450-3A4 enzyme- low
propensity for drug interactions
Plasma elimination half- life is 20 hours- longer duration
of action
No dosage adjustment required in elderly individuals
and patients with mild to moderate hepatic/ renal
insufficiency
8/13/2019 Razel (New) 25072013
28/31
Rosuvastatin: Salient Features
Excellent overall clinical efficacy Excellent efficacy in reducing LDL-C (Upto 65%
reduction- better than any other statin)
Most effective statin in increasing HDL-C
Substantial reduction in serum triglycerides
Percentage of patients achieving NCEP
treatment goals is very high
Well tolerated drug- Lowest rate of withdrawalthan other statins
Convenient dosage schedule- Once a day
administration during any time of the day.
8/13/2019 Razel (New) 25072013
29/31
Comparison of RAZEL with Atorvastatin
8/13/2019 Razel (New) 25072013
30/31
Comparison of RAZEL with Atorvastatin
8/13/2019 Razel (New) 25072013
31/31
TH NK YOU